Several converging lines of evidence support the hypothesis that the reinforcing properties of cocaine reside in its ability to augment mesolimbic dopamine transmission by blocking dopamine reuptake. In addition, alterations in dopaminergic functioning have been implicated in drug craving and anhedonia, which may contrbute to cocaine dependence. Therefor, it has been sugguested that drugs that alter dopaminergic neurotransmission may prove effective cocaine abuse. One possible therapeutic approach to cocaine dependence is the use of compaounds with high affinity for, and that dissociate slowly from. From the dopamine transfer. Such a compund would create a noncompeitive inhibition of the dopamine transporter and would render cocaine ineffective. The purposal is the examine the therapeutic potemtial of five affinity dopamine uptake inhibitors including RTI-31, RTI-32, RTI-176, RTI-177, and GBR 12909 using rodent models of drug abuse. The drug discrimination paradigm will be used in order to investigate whether these compounds produce cocaine-like subjective effects. The reinforcing properties of the drugs will be examined using conditioned place preference and drug seld-administration tasks to asses the incentive-motivational and response reinforcing effects of the compounds, respectively. Furthermore, because the reinforcing properties of a drug and its abuse are hypothesized to be greater for drugs that enter the brain and occupy receptor more rapidly, the studies proposed here will examine the relationship between the rate of drug entry into the brain of the DA uptake inbitors and its reforcing efficacy. Therefore, these stduies could yield a better understanding of the liabilty and pharmacotheruptic potenial of dopamine uptake inhibitors.